Balloon assemblies having controllably variable topographies

ABSTRACT

Various embodiments provide a device comprising a balloon assembly including a balloon, a film template, and a rigid element. The film template may have a fixed upper distension limit and may include at least one aperture. The rigid element may lay substantially flush with an outer surface of the balloon at a first inflated state of the balloon. The first upper distension limit of the balloon may be greater than the fixed upper distension limit of the film template and the balloon may outwardly protrude through the at least one aperture at a second inflated state. The rigid element may be extended in a radial direction away from the outer surface of the balloon as the balloon outwardly protrudes through the at least one aperture relative to the outer surface of the film template.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation application of U.S. application Ser.No. 13/645,414 filed on Oct. 4, 2012 and entitled “BALLOON ASSEMBLIESHAVING CONTROLLABLY VARIABLE TOPOGRAPHIES”, now U.S. Pat. No. 9,730,726,which claims priority to U.S. Provisional Application No. 61/545,039,filed on Oct. 7, 2011 and entitled “BALLOON ASSEMBLIES HAVINGCONTROLLABLY VARIABLE TOPOGRAPHIES”, wherein the above-listedapplications are hereby incorporated by reference in their entireties.

BACKGROUND OF THE DISCLOSURE Field of the Disclosure

The present disclosure relates generally to balloon assemblies havingcontrollable topographies and systems and methods relating to the same.

Discussion of the Related Art

Balloons intended for use within a mammalian body, such as a human, areemployed in a variety of medical procedures, including dilation ofnarrowed blood vessels, placement of stents and other implantabledevices, temporary or permanent occlusion of blood vessels, drugdelivery, thrombectomy, embolectomy, atherectomy, angioplasty, otherendovascular procedures, and other procedures within a lumen of amammalian body such as a human body. In this regard, as used herein, theterm “body” can comprise a mammalian body such as a human body or otheranimal body.

In a typical application, a balloon (often coupled with a catheter) isadvanced to the desired location in the vascular system or other lumenof the body. The balloon is then pressure-expanded in accordance with amedical procedure. Thereafter, the pressure is removed from the balloon,allowing the balloon to contract and permit removal of the catheter and,in many cases, the balloon.

Procedures such as these are generally considered minimally invasive,and are often performed in a manner which minimizes disruption to thepatient's body. As a result, balloons are often inserted from a locationremote from the region to be treated. For example, during angioplastyprocedures involving coronary vessels, the balloon catheter is typicallyinserted into the femoral artery in the groin region of the patient, andthen advanced through vessels into the coronary region of the patient.These balloons typically include some type of radiopaque marker to allowthe physician performing the procedure to monitor the progress of thecatheter through the body.

Non-compliant balloons are generally made of relatively strong butgenerally inelastic material (e.g., nylon, polyester, etc.), which mustbe folded to obtain a compact, small diameter cross section fordelivery. These relatively stiff balloons do not easily conform to thesurrounding vessel and thus can be used to compact hard deposits invessels. Due to the need for strength and stiffness, these devices arerated to employ high inflation pressures, usually up to about 4 to about60 atmospheres. As depicted in FIG. 1, non-compliant balloons (line C)have a maximum diameter, and as inflation fluid is introduced, suchballoons will not normally distend appreciably beyond a maximumdiameter. Once a non-compliant balloon is inflated to its maximumdiameter, the exertion of additional pressure can cause rupture of theballoon, creating a hazardous condition.

By contrast, compliant balloons generally comprise soft, elasticmaterial (e.g., natural rubber latex). As depicted in FIG. 1, compliantballoons (line A) will generally expand continuously in diameter andwill not appreciably increase in internal pressure as inflation fluid isintroduced. As a result, compliant balloons are generally rated byvolume (e.g., 0.3 cc) rather than by nominal diameter. Also, compliantballoons generally conform to the shape of the vessel. Althoughcomparatively weak compared to non-compliant balloons, compliantballoons have the advantage that they need not be folded about adelivery catheter (reducing profile) and tend to readily recompact totheir initial size and dimensions following inflation and subsequentdeflation. These balloons can be employed to displace soft deposits,such as a thrombus, where a soft and tacky material such as latexprovides an effective extraction means, and also can be used as anocclusion balloon, operating at low pressures.

In between the spectrum of compliant balloons and non-compliant balloonsfall semi-compliant balloons. As depicted in FIG. 1, semi-compliantballoons (line B) will both increase in pressure and increase indiameter as inflation fluid is introduced. However, semi-compliantballoons operate at pressures in between the two types of balloons andwill continue to distend as inflation fluid is introduced.

Both compliant and non-compliant balloons tend to have a uniform surfacetopography. In other words, conventional balloons tend to have smoothsurfaces. Balloons with more varied topographies may facilitate avariety of medical procedures and therapies not possible usingconventional balloons. For instance, a variable topography may provideincreased surface area over a similar conventional balloon, and thusinteraction with the body may be improved. A variable topography balloonmay also be configured to deploy sharp objects in a localized, difficultto reach part of the body, providing an improvement in therapy. Inaddition, variable topography balloons may provide improved drugdelivery systems. Moreover, it would be beneficial for a balloon to havea controllable topography.

SUMMARY OF THE DISCLOSURE

The present disclosure provides systems and methods for balloonassemblies having varied topographies and pre-configured surfacetextures. In various embodiments, a device is provided comprising aballoon comprising a size limiting layer and a template disposed aroundor within the balloon. The template comprises at least one aperture anda portion that is more resistant to deformation in a radial directionthan the balloon or the size limiting layer, either because templatecomprises a less compliant material or has an upper distension limitthat is less than the size limiting layer's upper distension limit. Assuch, the balloon and size limiting layer are configured to distendbeyond the template about the aperture at a given volume/pressure. Theballoon and size limiting layer will distend about an aperture to asecond inflated state comprising a varied topography. The size limitinglayer prevents further appreciable distension beyond the second inflatedstate. In various embodiments, the template and/or balloon canoptionally comprise an expanded polytetrafluoroethylene (ePTFE). Theballoon and/or template can comprise a tape wrapped membrane. Otherembodiments comprise methods of making and using the same.

In various embodiments, a balloon assembly is provided comprising aballoon having a controlled topography, wherein the balloon assembly hasa smooth or substantially wrinkle free surface at a first inflated stateand a varied topography surface at a second inflated state. In anembodiment wherein the balloon assembly comprises an inner balloon andan outer template, the inner diameter of the template at a firstinflated state is substantially equal to the outer diameter of theballoon at a first inflated state. In an embodiment wherein an outerballoon is disposed around an inner template, the converse is true;namely, the outer diameter of the template at a first inflated state issubstantially equal to the inner diameter of the balloon in the firstinflated state. The balloon and/or template can comprise a tape wrappedmembrane. Other embodiments comprise methods of making and using thesame.

In other embodiments, a balloon assembly can comprise an underlyingcompliant balloon and an overlying less compliant template having atleast one aperture. Located within the aperture can be a therapeuticagent, preferably in a solid or viscous form. Upon inflation, theunderlying compliant balloon will protrude through the aperture andconvey the therapeutic agent external to the template. In this manner, atherapeutic agent can be delivered to a surrounding tissue such as theintima of a vessel. Other embodiments include methods of making andusing the same.

Another aspect of the present disclosure comprises textured balloonassemblies. In various embodiments, a balloon can be covered and/orwrapped with a textured network that provides a topographical feature.For example, a textured network can comprise beads, filaments, fibers,rings, knits, weaves, and/or braids, which can be wrapped or otherwisedisposed over or within a balloon. The textured network creates raisedsurface patterns that can provide therapeutic effect. Other embodimentsinclude methods of making and using the same.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings are included to provide a furtherunderstanding of the present disclosure and are incorporated in andconstitute a part of this specification, illustrate embodiments of thepresent disclosure, and together with the description serve to explainthe principles of the disclosure.

FIG. 1 compares pressure to height of complaint balloons (Line A),semi-compliant balloons (Line B), and non-compliant balloons (Line C);

FIG. 2A illustrates a schematic varied topography balloon assemblyembodiment from a cross-sectional perspective;

FIGS. 2B(1) to 2B(3) illustrates a varied topography balloon assemblyembodiment of the present disclosure in a deflated state; a firstinflated state; and a second inflated state;

FIG. 2B(4) illustrates a close up, cross-sectional view about anaperture of a varied topography balloon assembly embodiment illustratedin FIG. 2B(3);

FIGS. 3A(1) to 3A(3) schematically illustrate the process under whichvarious embodiments distend to a second inflated state thereby forming avaried topography balloon assembly;

FIGS. 3B(1) to 3B(3) schematically illustrate the process under whichvarious embodiments distend to a second inflated state thereby forming avaried topography balloon assembly;

FIGS. 4A to 4D illustrate wrapping a film tape to form a size limitingmembrane layer;

FIG. 5A schematically illustrates a balloon assembly embodimentcomprising a tapered balloon and/or size limiting layer;

FIG. 5B schematically illustrates a balloon assembly embodimentcomprising a tapered template;

FIGS. 6A and 6B illustrate a cross-sectional view of a varied topographyballoon assembly embodiment wherein a plurality of apertures are locatedon a first section of the template and no apertures are located on asecond section of template;

FIG. 7 A schematically illustrates a varied topography balloon assemblyembodiment of the present disclosure comprising two templates;

FIG. 7B illustrates a close up, cross-sectional view about an apertureof a varied topography balloon assembly embodiment illustrated in FIG.7A;

FIG. 8 illustrates a varied topography balloon assembly comprising atherapeutic agent, in accordance with various embodiments;

FIG. 9 illustrates a varied topography balloon assembly embodimentwherein the balloon comprises a wall with regions of reduced compliancethan other more distensible regions;

FIG. 10A illustrates a cross-sectional view of a balloon assemblyembodiment wherein the overlying template comprise rigid elements;

FIG. 10B illustrates a cross-sectional view of a balloon assemblyembodiment depicted in FIG. 10A with the rigid elements outwardlyrotated;

FIG. 10C illustrates a cross-sectional view of a balloon assemblyembodiment wherein the overlying template comprises rigid elementshaving a piercing or sharp tip that is attached to template at itsproximal base;

FIG. 10D illustrates a cross-sectional view of a balloon assemblyembodiment wherein the overlying template comprises rigid elements ofFIG. 10C outwardly rotated;

FIG. 10E illustrates a cross-sectional view of a balloon assemblyembodiment wherein the overlying template comprises rigid elementshaving a lumen therethrough which is in fluid communication with theballoon;

FIG. 11 illustrates a inflated balloon assembly comprising a wiretemplate;

FIG. 12 illustrates a balloon assembly in accordance with variousembodiments within the vasculature;

FIGS. 13A to 13C illustrate a textured balloon assembly in accordancewith various embodiments;

FIG. 13D illustrates a cross sectional view a textured balloon assemblyon a mandrel, in accordance with various embodiments;

FIG. 14A illustrates a deflated balloon assembly with a scored templatepattern from an exterior perspective, in accordance with variousembodiments;

FIG. 14B illustrates an inflated balloon assembly with a deployed scoredtemplate pattern from an exterior perspective, in accordance withvarious embodiments;

FIG. 14C(1) illustrates a close-up, perspective view of a deflatedballoon assembly with an arced element across the aperture of atemplate, in accordance with various embodiments;

FIG. 14C(2) illustrates a close-up, perspective view of an inflatedballoon assembly with a deployed arced element across the aperture of atemplate, in accordance with various embodiments;

FIG. 14C(3) illustrates a close-up, side view of the inflated balloonassembly of FIG. 14C(2), in accordance with various embodiments;

FIG. 14D(1) to 14D(4) illustrate the various patterns of templatecomprising an arced element across the aperture;

FIG. 14E(1) illustrates a close-up, perspective view of a deflatedballoon assembly with an arced element across the aperture of atemplate, in accordance with various embodiments;

FIG. 14E(2) illustrates a close-up, perspective view of the inflatedballoon assembly of FIG. 14E(1), in accordance with various embodiments;

FIG. 15 illustrates a method of making, in accordance with variousembodiments;

FIG. 16 illustrates a method of use, in accordance with variousembodiments;

FIG. 17 illustrates a balloon assembly embodiment wherein a template islocated on an intermediate section of a balloon;

FIG. 18 illustrates a balloon assembly embodiment wherein the balloonand size limiting layer is perfusable;

FIGS. 19A-B illustrates a varied topography balloon assembly embodimentwherein the balloon comprises a wall with regions of reduced compliancethan other more distensible regions;

FIGS. 20A-20B illustrates a varied topography balloon assembly with astent device mounted thereon, the stent device having deployable anchorswhich are actuated by protruding apertures; and

FIG. 21 illustrates a varied topography balloon assembly wherein anaperture or a plurality of apertures are located on a circumferentialsection.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

Persons skilled in the art will readily appreciate that various aspectsof the present disclosure can be realized by any number of methods andapparatuses configured to perform the intended functions. Stateddifferently, other methods and apparatuses can be incorporated herein toperform the intended functions. It should also be noted that theaccompanying drawing figures referred to herein are not all drawn toscale, but can be exaggerated to illustrate various aspects of thepresent disclosure, and in that regard, the drawing figures should notbe construed as limiting. Finally, although the present disclosure canbe described in connection with various principles and beliefs, thepresent disclosure should not be bound by theory.

As used herein, “balloon assembly” means a balloon coupled with one ormore other components, such as a template (described herein), sizelimiting layer (descried herein), catheter, distal cap (“olive”), cover,or other apparatus.

As used herein, the term “size limiting” means that a material orcomponent has an upper distension or deformation limit beyond which amaterial or component will not appreciably expand, distend, and/ordeform. For example, a size-limited balloon can be inflated to a maximumdiameter, and once this diameter is reached, further increases inpressure will not cause an appreciable increase in its diameter. Asreflected in FIG. 1, a non-compliant balloon (line C) is a size-limitedballoon, and traditional compliant (line A) and semi-compliant (line B)balloons are not size-limited balloons. Accordingly, a “compliantballoon,” as used herein, refers to both compliant and semi-compliantballoons or balloons that are not size limited, but will continue toexpand, distend, and/or deform as the internal pressure increases untilthe point of failure, e.g., the balloon wall ruptures. In accordancewith certain embodiments of the present disclosure, the described“compliant” balloons are referred to as such because the describedballoons generally conform to the shape of their surroundings (e.g., asurrounding anatomy or vessel) like traditional “compliant” balloons,e.g., portions of the described “compliant” balloons are able tooutwardly extend from the template to form protrusions.

As used herein, the term “to inflate” can mean to fill or causeexpansion by introducing a flowable substance (e.g., an influx offluid), such as a liquid (e.g., saline), a gel, or a gas.

As used herein, the term “inflated” means a balloon at an internalpressure or volume above the internal pressure or volume at which theballoon begins to expand from a deflated state. As used herein, a “firstinflated state” refers to an inflated balloon at a first pressure orfirst volume which will result in a balloon with a generally smooth oruniform surface, except perhaps with respect to slight recesses at thesite of the aperture(s). As used herein, a “second inflated state”refers to an inflated balloon at a second pressure or second volumegreater than the first pressure or first volume which will result in aballoon with a varied topography. As used herein, “varied topography”refers to a balloon assembly surface that has textured, bumpy, ribbed,or other three-dimensional surfaces.

As used herein, the term “elongate element” is generally any elementconfigured for relative axial movement with an endoluminal devicedelivery element (e.g., a catheter-based endoluminal device deliveryelement such as a balloon catheter) and includes any longitudinallyextending structure with or without a lumen therethrough. Thus, elongateelements include but are not limited to tubes with lumens (e.g.,catheters), solid rods, hollow or solid wires (e.g., guidewires), hollowor solid stylets, metal tubes (e.g., hypotubes), polymer tubes, pullcords or tethers, fibers, filaments, electrical conductors, radiopaqueelements, radioactive elements and radiographic elements. Elongateelements can be any material and can have any cross-sectional shapeincluding, but not limited to, profiles that are elliptical,non-elliptical, or random.

As described herein, balloon assemblies used inside the body generallyinteract with the body through contact with an exterior surface of theballoon assembly. Thus, the surface topography of a balloon assembly canaffect the physical interaction between the balloon assembly and thebody or a device inside the body. The ability to control a balloon'stopography, or three dimensional surface characteristics, allows balloonassemblies to interact with the body in new or improved modes. Variousadvantages can be realized using controllably variable topographyballoon assemblies. For example, balloon assemblies, such as those thatcan be used with a catheter, can be inserted into a lumen of the body.The balloon assembly can interact with the body in a variety of wayswhich can be facilitated by designing topographies which yield improvedresults. In this regard, for example, a balloon having a variedtopography can improve engagement with a vessel wall and/or improveatherosclerotic plaque or thrombus removal ability, such from a vesselwall or the wall of an endoprosthesis.

By selectively constraining the expansion of a balloon at selectedsites, the balloon assembly topography can be varied. For example, withreference to FIG. 2A, a schematic of a balloon assembly 200 is shown.FIGS. 2B(1) to 2B(3) illustrate a varied topography balloon 200 in adeflated state (FIG. 2B(1)), a first inflated state having a generallyuniform or smooth surface (FIG. 2B(2)), and a second inflated statehaving a varied topography (FIG. 2B(3)). FIG. 2B(4) illustrates aclose-up, cross-sectional view of a protrusion 212 of a variedtopography balloon 200.

Balloon assembly 200 comprises balloon 210 and template 220. Balloon 210can be disposed along template 220, either underlying or overlying thetemplate 220. The balloon 210 may comprise a working length and at leastone tapered section (i.e., a shoulder). The template 220 may extendalong at least a portion of the working length of the balloon 210. Thetemplate 220 may also extend along at least a portion of at least oneshoulder of the balloon 210. Assembly 200 can further comprise acatheter 202 to which balloon 210 and template 220 are attached.Catheter 202 is shown in fluid communication with balloon 210, such thatfluid can be introduced through catheter 202 into balloon 210. Catheter202 can be coupled to any suitable medical device, such as a syringe, anindeflator, pump or any other apparatus for conducting fluid throughcatheter 202 and into balloon 210.

Template 220 can be an overlying or underlying structure comprising atleast one aperture 221. Template 220 constrains a portion of balloon 210during inflation. In this regard, balloon 210 is inflated to a secondinflated state, and the restraining action of template 220 causesballoon 210 to distend at apertures 221 in template 220 as described inmore detail below.

The operation of the balloon assemblies of the present disclosure isshown schematically for various embodiments in FIGS. 3A(1) to 3A(3) and3B(1) to 3B(3) in which is illustrated a longitudinal cross section of aballoon assembly 300. In FIGS. 3A(1) to 3A(3), balloon 310 underliestemplate 320 which features apertures 321. In FIGS. 3B(1) to 3B(3),balloon 310 overlies template 320, and template 320 adheres to balloonduring inflation. In these illustrations, balloon 310 and template 320are shown aligned with axis “A”. Axis “A” can comprise the longitudinalaxis of a catheter.

A first inflated state is shown in FIGS. 3A(2) and 3B(2). With referenceto FIG. 3A(2), balloon 310 has an outer radius shown as “R1” undertemplate 320, and template 320 has an inner radius of “R2”. Withreference to FIG. 3B(2), balloon 310 has an inner radius shown as “R1”over template 320, and template 320 has an outer radius “R2”. In thefirst inflated state, radius “R1” is substantially equal to radius “R2”.No protrusions are observed in a first inflated state. Stateddifferently, the height, “H1” of balloon material or protrusions abovetemplate 320 has a value of zero or close to zero. At the first inflatedstate, balloon 310 comprises a substantially smooth or wrinkle freesurface. Also in the first inflated state, aperture 321 has a widthshown as “W1” in the figures.

FIGS. 3A(3) and 3B(3) depict balloon assembly 300 in a second inflatedstate. As balloon 110 is inflated beyond a first inflated state, radius“R2” increases relative to radius “R1” about aperture 321. This isbecause balloon 310, upon distention, begins to distend about orprotrude from or above apertures 321. Radius “R1” remains essentially atthe same dimension as in the first inflated state shown FIGS. 3A(2) and3B(2). In some embodiments, width of aperture 321 (“W2”) remains closeto or even equal to width of aperture 221 (“W1”) in the previousinflated state shown in FIGS. 3A(2) and 3B(2). In other embodiments, W2can be greater than W1; i.e., aperture 320 can increase in size asballoon assembly 300 is inflated. It will be understood that radius “R2”can be a maxima, in particular if a size limiting layer or a sizelimited balloon is used as described below.

Referring again to FIGS. 2A and 2B(1) to 2B(4), in various embodiments,balloon 210 can comprise any suitable compliant balloon. As describedabove, a compliant balloon can comprise a polymeric material. Exemplarymaterials for a compliant balloon include elastomers such aspolyurethane and silicone, natural rubber or latex products, syntheticrubber such as nitrile butadiene, or other synthetic or naturallyoccurring polymeric materials. In various embodiments, balloon 210 maynot be fully compliant, but is more compliant than template 220 andsufficiently flexible to inflate to a diameter larger than therestraining template 220 diameter at a given pressure, and therebyproduces protrusions 212 (as described below). Thus, a semi-compliant ornon-compliant balloon can be used. In various embodiments, balloon 210can be conditioned. Conditioning can comprise stretching, pre-inflating,blow molding, heating, or other process to render the balloon 210 moreamenable to use.

In various embodiments, balloon assembly 200 can comprise balloon 210,template 220, and a size limiting layer 215. Similarly, balloon 210 cancomprise a composite material, wherein a layer of the composite is sizelimiting layer 215 and/or template 220. Size limiting layer 215 can bedisposed about balloon 210, either between balloon 210 and template 220or around template 220. Similar to template 220, size limiting layer 215is configured to control the degree of distension of a compliant balloon210 during inflation. However, size limiting layer 215 is configured topermit a degree of distension which is greater than the degree thattemplate 220 is configured to permit. In this regard, size limitinglayer 215 can possess sufficient flexibility and an upper distensionlimit which is larger in diameter than the restraining template 220diameter at a given pressure, allowing size limiting layer 215 todistend about or protrude through aperture 221. In addition, sizelimiting layer 215 can be configured to have a substantially smooth orwrinkle free surface at the first inflated state. Stated differently,size liming layer is at least slightly strained at the first inflatedstate.

Size limiting layer 215 can be a sheath, sleeve, layer or othercomponent otherwise configured to at least partially enclose all or aportion of balloon 210. Size limiting layer 215 can act to constrainballoon 210 in a substantially uniform manner once balloon 210 distendsto a certain diameter or dimension. Size limiting layer 215 can beconfigured to operate at pressures of up to 2 atm, up to 5 atm, up to 10atm, up to 15 atm, up to 20 atm, up to 30 atm, up to 35 atm, up to 45atm, up to 55 atm, up to 60 atm, or up to any value between about 2 atmand about 60 atm.

In various embodiments, size limiting layer 215 can comprise anyflexible, preferably thin material which is inelastic in at least oneorientation or has a suitable upper deformation limit in at least oneorientation. To withstand higher inflation pressures, size limitinglayer 215 can be made of a high strength material. Size limiting layer215 can be constructed using any material described herein forconstructing template 220. Size limiting layer 215 can be an extruded ormolded tubular form which is at some point inelastic in acircumferential direction. Alternatively, size limiting layer 215 cancomprise a tape wrapped form wherein the tape is, at some point,inelastic or has an upper distension limit in the tapes lengthwisedirection.

To form tape-wrapped size limiting layer 215, with reference to FIG. 4Ato 4D, a thin film can be slit into relatively narrow widths to form atape. The tape is helically wrapped onto the surface of a mandrel 12 intwo opposing directions 20 and 22, thereby forming a tube of at leasttwo layers 14 and 16. Both layers 14 and 16 can be wrapped with the samepitch angle measured with respect to the longitudinal axis 18 butmeasured in opposite directions. If, for example, the film layers 14 and16 are applied at pitch angles of 70° measured from opposite directionswith respect to the mandrel's longitudinal axis 18, then included angleA between both 70° pitch angles is 40°.

More than two layers of helically wrapped film may be applied. Alternatelayers of film can be wrapped from opposing directions and an evennumber of film layers can be used whereby an equal number of layers areapplied in each direction.

Suitable adhesives may be used to join film wraps together. Suchadhesives include fluorinated ethylene propylene (FEP). Alternatively,following completion of film wrapping, the helically wrapped mandrel 12can be thermally treated at suitable time and temperature to causeadjacent layers 14 and 16 to heat-bond together. Regardless of bondingmethodology, the size limiting layer 415 is removed from mandrel 12 andcan be placed over the balloon, tensioned longitudinally as needed andaffixed in place over the balloon.

During inflation of balloon, size limiting layer 415 can undergo anincrease in diameter which results in included angle A beingsubstantially reduced as shown by FIG. 4D. Size limiting layer 415 thusreaches its pre-determined upper distension limit as included angle Aapproaches zero. This pre-determined limit is greater than thedistension limit of template in order to yield a balloon having a variedtopography at a second inflated state but one which does not appreciablydistend beyond the second inflated state.

Again with reference to FIGS. 2A and 2B(1) to 2B(4), size limiting layer215 can optionally be adhered to or laminated with balloon 210. Ifadhered, balloon 210 can aid in recompaction of size limiting layer 215upon deflation of balloon assembly 200, in particular if balloon 210 ismade of an elastomeric materiel. Alternatively, a layer of elastomer,applied to a surface of size limiting layer 215 will cause the sizelimiting layer 215 to retract substantially to its pre-inflation size asshown by FIG. 4C following deflation.

The film utilized to construct size limiting layer 215 as describedabove can comprise any flexible, preferably thin material that issubstantially inelastic or has an upper distension limit in at least oneorientation and has sufficient strength to yield a balloon 210 that canoperate at pressures of up to 2 atm, up to 5 atm, up to 10 atm, up to 15atm, up to 20 atm, up to 30 atm, up to 35 atm, up to 45 atm, up to 55atm, or up to 60 atm. For example, a film can comprise ePTFE. Othersuitable film materials can include other fluoropolymers ornon-compliant polymers.

In various embodiments, size limiting layer 215 can be constructed orconditioned to constrain balloon 210 upon inflation to a generallycylindrical inflation profile. Optionally, with momentary reference toFIG. 5A, size limiting layer 515 can be configured to alter the generalprofile of balloon 510, e.g., constrain to create a tapered profile,elliptical profile, or a dumbbell profile. In addition, in the event ofa failure of balloon 210 (e.g., a rupture), size limiting layer 215 canact to prevent release of undesired debris from the disrupted balloonassembly 200.

In other embodiments, size limiting layer 215 and balloon 210 arecombined into a single component. Stated differently, balloon 210 cancomprise a compliant, size limiting material. In such embodiments,balloon 210 behaves like a compliant or semi-compliant balloon up to adesired diameter. Once the desired diameter is reached, balloon 210behaves like a non-compliant balloon, allowing the pressure to increasewithout resulting in an appreciable increase in a balloon dimension.

In various embodiments, template 220 comprises any size-limited formthat acts to constrain balloon 210 along the points of contact.Alternatively, template 220 can comprise a form less compliant thanballoon 210 and/or size limiting layer 215 so that balloon 210 isconstrained along the points of contact. As such, template 220 isconstructed of any material that cannot be appreciably deformed beyond afirst inflated state during inflation of balloon 210. Template 220 canbe configured as a sleeve, layer, or sheath positioned over balloon 210.For example, template 220 can comprise a generally cylindrical,ellipsoidal, spherical, or similar form that is disposed substantiallycoaxial to balloon 210. Alternatively, template 220 can be an innerlayer that constrains a portion of balloon 210 by being adhered toballoon 200 at selected portions not comprising an aperture 221.

In addition, while aperture 221 of template 220 can be spatiallyconfigured to create a varied topography, the constraining portion oftemplate 220 can also impact the general profile of balloon 210. Forexample, as illustrated in FIG. 5B, template 520, at a first inflatedstate, can have a diameter that is larger or smaller at differentlocations along the balloon 510, for instance to form a taper. Thus,while balloon 510 can inflate in the shape of a cylinder, template 520can have a non-cylindrical shape, and this non-cylindrical shape can bethe general profile of balloon assembly 500. Such a generally taperedprofile can be used to better conform to cardiovascular vessel diameterswhich change over length, for example. In addition, the lesion orthrombus “scraping” effect of the assembly 500 can be intensifiedproximally to distally or visa versa due to the varying profiledimensions.

Returning to FIGS. 2A and 2B(1) to 2B(4), template 220 does notsubstantially deform beyond a first inflated state or deforms to alesser extent than balloon 210 and size limiting layer 215 in responseto inflation of balloon 210. As depicted in FIGS. 2B(3) and 2B(4),balloon 210 and size limiting layer 215 distends beyond template 220about aperture 221 creating a protrusion 212 at a second inflated state.As shown, at the second inflated state, inflated balloon assembly 200can have a varied topography in that the surface of balloon assembly 200has a plurality of peaks and valleys.

In various embodiments, template 220 can comprise a size-limitedmaterial or configuration. For example, template 220 can besubstantially inelastic in at least one direction or orientation,preferable a direction transverse to the longitudinal axis of balloonassembly 200 and, in various embodiments, template 220 can also comprisea material that has high tensile strength in at least one direction. Inan alternate embodiment, the template can comprise a material that has ahigh strength in both directions so as to prevent the perimeters ofapertures 221 from deforming upon expansion of balloon 210. In variousembodiments, template 220 can comprise a material that is less compliantthan balloon 210 and/or template; thus, at a given pressure, balloon 210will have a greater degree of distension than template 220.

In an embodiment, template 220 can comprise a high strength, yetflexible material such as ePTFE. High strength provides resistance todeformation in at least one direction such that template 220 can resistexpansion of underlying balloon portions beyond the application of aparticular force caused by balloon inflation pressures.

In various embodiments, template 220 can be made from a thin, highstrength film or tape to forming a template. For example, template 220can be constructed from a type of ePTFE as described in U.S. Pat. No.7,306,729, issued Dec. 11, 2007 and entitled, “Porous PTFE Materials AndArticles Produced Therefrom,” whose contents are herein incorporated byreference. In various embodiments, two to sixty layers of ePTFE asdescribed in U.S. Pat. No. 7,306,729 can comprise template 220. Layerscan be circumferentially (i.e., wrapped at about 90° to the longitudinalaxis) or helically wrapped (as described previously). In variousembodiments, template 220 can be manufactured in a continuous processand then cut to the desired length before being disposed on balloons.Optionally, template 220 can be adhered or laminated to balloon 210and/or size limiting layer 215.

Template 220 can comprise other materials, such as other fluoropolymers,including polytetrafluoroethylenes with different microstructures fromthat described in U.S. Pat. No. 7,306,729, so long as they providesufficient strength and relative lack of compliancy, to produce thedesired balloon topography and operate at the previously describedpressure thresholds.

In various embodiments, template 220 can also be size-limited butcompliant. In such embodiments, template 220 can be formed in a similarmanner as size-limited layer and compliant balloon 210. However, inorder to create a varied topography, the upper distension limit oftemplate 220 must be less than the upper distension limit of the balloon210 or the degree of compliancy is less than that for balloon 210.

Template 220 can comprise at least one aperture 221 and, in variousembodiments, template 220 can comprise an aperture pattern and/or aplurality of apertures. Apertures 221 can be present in template 220prior to inflation or be formed or increase in size upon inflation.

Aperture 221 can comprise an opening or weakened site in the templatematerial. In this regard, an opening can be a hole, cut, or any otherdiscontinuous section of the template material. For example, a holecould be formed by puncturing template 220. Alternatively, aperture 221can comprise an area of template 220 where a portion of the material hasbeen removed or otherwise weakened such that the weakened portion atleast partially deforms or detaches in response to inflation of balloon210 and permits distension beyond the first inflated state. Apertures221 can be formed by any suitable means, including cutting, stamping,laser cutting, perforating, and/or punching/puncturing and/or the like.In various embodiments, template 220 can comprise a net like structure.

Optionally, template can comprise apertures that vary in size.Increasing the size the apertures can allow for a wider (or “coarser”)protrusion. By combining varying aperture sizes with a tapered templateprofile, as shown in FIG. 5B, the “scraping” effect of the assembly canbe intensified proximally to distally or visa versa due to the differentprotrusion heights.

With reference again to FIGS. 2A and 2B(1) to 2B(4), template 220 can beconfigured such that apertures 221 are formed or increase in size uponinflation. For example, a template 220 comprising a tape wrapped, woven,or braided membrane around balloon 210 can be constructed, e.g. wrapped,woven, or braided, such that apertures 221 are formed by leaving a spacebetween tape edges and/or apertures 221 form or increase in size betweentape edges upon inflation of balloon 210. In an embodiment, the angle ofthe tape material can change relative to the longitudinal axis of theballoon upon inflation and/or the tape material can narrow in width asthe balloon assembly is expanded, thus creating apertures 221.

In addition, the varied topography can vary longitudinally along thelength of the balloon and/or can vary circumferentially about theperimeter of the balloon. For example, with reference to FIG. 6(A-B),balloon assembly 600 can comprise a template 620 having a first patternof apertures 621 on first section 650 of balloon 610 and a secondpattern of aperture or zero apertures on a second section 651.Similarly, the longitudinal and/or circumferential variation can berandom or follow a pre-defined pattern. Such balloon assemblies can beused for performing interventional procedures in combination. Forexample, such a balloon configured with zero apertures on one half thelength of the balloon assembly and apertures on the remainder of theassembly can be used to perform both thrombectomy (with the aperturedportion of the assembly) then Percutaneous Transluminal Angioplasty(PTA) (with the non-apertured portion), all without the exchange ofdevices.

The balloon assembly can be selectively alternated between the variousinflated states, e.g., between a first inflated state and a secondinflations state. A specific inflated state can be determined bymeasuring the volume injected into balloon assembly and/or pressurelevels within balloon assembly. By selectively introducing orwithdrawing a fluid by a predetermined amount, balloon assembly cantransition from one inflated state to another. In an embodiment, theballoon assembly can be configured to pulsate between the variousinflations states.

In various embodiments, balloon assembly can optionally comprise aprotective cover. A protective cover can be a sleeve or sheath thatcovers at least a portion of template. The protective cover can bedelivered with the balloon assembly into the body and be retracted toexpose balloon assembly 200 while within the body.

With the described components, one can adapt the compliance of theballoon, a template, an aperture pattern, inflation pressures andextensibility of a size limiting layer to control the topography of aballoon assembly. For example, an aperture pattern can comprise manysmall apertures to obtain a “fine texture” pattern or can comprise fewerlarger openings to obtain a more “coarse texture” pattern. As one canappreciate, any possible aperture pattern, or combinations of aperturepatterns, is contemplated herein. For example, a first portion of atemplate can comprise a square grid like aperture pattern and a secondportion of a template can comprise a diamond shaped pattern.

In other embodiments, a balloon expanding through a template can defineridges and troughs which, for example, run parallel to the longitudinalaxis of the balloon. In one embodiment, these provide for bloodperfusion between balloon and vessel wall during a treatment when theballoon is expanded.

In other embodiments, protrusions 212 can form at a first inflated stateas depicted in FIG. 2C, and then upon inflation to a second inflatedstate, having a pressure greater than the first, template 220 candistend and the surface of balloon 210 is smooth, as depicted in FIG.2B. In an embodiment, template 220 can be partially or selectivelydistensible. For example. a 4 mm template that is distensible up to 8 mmcan overlay a balloon and/or a size limiting layer. Balloon 210 isinflated to 2 atm and the template acquires its first distension profileso that protrusions form. Upon further inflation up to 4 atm, thetemplate can distend to its second distension profile or its maximumsize. The maximum size of template 220 can correspond to the maximumsize of balloon 210 and/or size limiting layer 215. In otherembodiments, template 220 can be frangible and made to break or stretchat a selected inflation pressure to then reduce the height, at leastpartially, of some or all of protrusions 212 to allow for increasedcontact between the balloon surface and the target tissue(s) at a higherpressure. Such embodiments can be used to perform both thrombectomy (atthe first inflated state) then Percutaneous Transluminal Angioplasty(PTA) (at the second inflated state), all without the exchange ofdevices.

In various additional embodiments, multiple templates can be used withone compliant balloon to further control and further vary topography.With reference to FIGS. 7A and 7B, balloon assembly 700 comprisesballoon 710 and at least two templates 720 and 725. Template 720 can bedisposed coaxially or substantially coaxially over balloon 710, andsecondary template 725 can be disposed coaxially or substantiallycoaxially over template 720. Upon inflation of balloon 710 to the secondinflated state, as depicted in FIG. 7A, both template 720 and secondarytemplate 725 act to constrain balloon 710 and have aperture patterns toallow balloon 710 to expand through apertures 721 in each template. Inan embodiment, template 720 and secondary template 725 can act to shapethe topography of inflated balloon assembly 700. Template 720 can createa “coarse” varied topography, and secondary template 725 is selectivelypositioned to constrain a portion of protrusion 712 and create a “fine”aperture pattern. Protrusion 712 is thus further constrained bysecondary template 725 to form at least two protrusions or protrusionsof different size or shape and create a finer or varied aperturepattern.

Optionally, each template can have different upper distension limitssuch that the varied topography can vary by varying the distension ofballoon 710. In such embodiments, balloon assembly 700 can have three ormore inflated states. It is contemplated that any number of templatescan be layered in a balloon assembly to vary and refine topography. Inaddition, balloon assembly 700 can optionally comprise a size limitinglayer as described herein.

FIG. 9 and FIG. 18 illustrate a varied topography balloon assemblyembodiment wherein the balloon comprises a wall with regions of reducedcompliance than other more distensible regions;

With reference to FIG. 18, balloon 1810 can comprise a wall havingportions 1817 of reduced or less compliance than other, more distensibleportions 1818 of wall. The other portions 1818 being essentially the“apertures” that expand outwardly relative to the portions of reduced orless compliance. The more distensible portions 1818 can comprise anupper distension limit. The portions 1817 of reduced compliance can beformed through laser densification or by imbibing with a polymer thatreduces the compliance in the imbibed region. In an embodiment, theregions 1817 of reduced compliance have substantially the same thicknessas the more distensible regions 1818. Similar, with other embodimentsdescribed herein, balloon 1810 can be formed via tape wrapping orextrusion, and can comprise ePTFE or any other material wherein thecompliancy can be varied at discrete sites.

Similarly, in an embodiment, the balloon can comprise a plurality ofprotrusions in the form of knob-like features. Unlike the previouslydescribed embodiment, the distensiblity of the sites need not vary alongthe balloon material. Here, the protrusion is pre-formed into theballoon. To form a knob-like feature on the balloon, a balloon form canbe placed onto a mandrel or constructed on a mandrel which has anaperture or recessed site thereon corresponding to the site of aknob-like feature. In an embodiment, a heated element can be used topush the knob-like feature into the aperture or recess and set thefeature into the balloon wall. Similarly, a lower melt thermoplasticmaterial can be imbibed into the balloon wall at the site of the recessand aperture with the application of pressure and heat, and allowed tocure while pressure is still applied and the wall is recessed. Inanother embodiment, a vacuum can be applied to the apertures (orpressure applied to the balloon) such that a recessed site is formed onthe balloon surface. The balloon can then be cured while in thisconfiguration.

In further embodiments, with reference to FIG. 19, balloon assemblies1900 as described herein can be perfusable. For example, balloon 1910,size limiting layer 1915, and optionally, template 1920 can comprise aporous material. In addition, balloon 1910, size limiting layer 1915,and optionally, template 1920 can comprise a variably perfusablematerial. In various embodiments, prior to protrusion, the porosity ofthe material or the internal pressure is low enough to not perfuse orminimally perfuse. For example, upon expansion of balloon 1910 and itsprotrusion through apertures 1921, localized forces can cause themicrostructure of the material protruding through apertures 1921 tobecome more porous, allowing the therapeutic agent to be released fromballoon 1910. In other embodiments, the porosity of the microstructureis not altered but rather the water entry pressure of the balloonmaterial is such that the balloon does not perfuse until a certainthreshold pressure. As such, balloon 1919 can be configured not toperfuse until the second inflated state is obtained. In addition,balloon 1910 can be configured to perfuse along only a portion, e.g.,the regions of balloon 1910 that upon inflation, protrude throughapertures 1921.

In various embodiments, a balloon assembly can further comprise atherapeutic agent disposed on, inside of, temporarily filling, orotherwise be integrated with the template. Similarly, a balloon assemblycan comprise a therapeutic agent disposed on an inner or outer surfaceof the balloon or template, or inside balloon. In an embodiment, atherapeutic agent can be coated on a portion of the elongate memberunderlying the balloon. Therapeutic agent formula can comprise a liquidor solid form. Liquid from can be of a desired viscosity suitable forthe treatment desired.

With reference to FIG. 8, balloon assembly 800 comprises balloon 810disposed within template 820, and therapeutic agent 808 is disposedbetween balloon 810 and template 820. Upon inflation of balloon 810,therapeutic agent 808 can be conveyed through an aperture 821 oftemplate 820 and be released at a localized portion of the body. In anembodiment, aperture 821 can form upon inflation thus containingtherapeutic agent 808 until balloon assembly 800 is inflated.

Similarly, therapeutic agent can be disposed within aperture. Uponinflation of balloon, therapeutic agent can be conveyed beyond apertureby protrusion and be directed to a surrounding tissue and/or a localizedportion of the body. In various embodiments, the therapeutic agentformula can be in a solid or viscous form to maintain location withinaperture. Alternatively, therapeutic agent, positioned within aperturecan be protected by a sheath until placed at a treatment site whereuponthe sheath can be retracted.

In addition, aperture can be configured to limit the release oftherapeutic agent until inflation is underway. For example, aperturescan comprise a conical or other tapered shape, wherein the aperturedefines a smaller area on the outer face than on the inner face.Aperture can be configured to enlarge upon inflation to facilitaterelease of therapeutic agent. In addition, balloon assembly can comprisea releasable cover to limit or prevent the release of therapeutic agent.

Any therapeutic agent that aids in any procedure, e.g., diagnostic ortherapeutic procedures, or that aids in providing a therapeutic and/orcurative effect is contemplated and suitable for use with balloonassemblies disclosed herein. In particular, therapeutic agents thatbecome safer, effective, or achieve another benefit from localizeddelivery are useful with balloons disclosed herein. Among others,suitable therapeutic agents include anti-proliferative,anti-inflammatory, fibrolytic, thrombolytic, anti-phlogistic,anti-hyperplastic, anti-neoplastic, anti-mitotic, cytostatic, cytotoxic,anti-angiogenic, anti-restenotic, microtubule inhibiting, anti-migrationor anti-thrombotic therapeutic agents.

For example, suitable therapeutic agents can include: abciximab,acemetacin, acetylvismione B, aclarubicin, ademetionine, adriamycin,aescin, afromoson, akagerine, aldesleukin, amidorone, aminoglutethemide,amsacrine, anakinra, anastrozole, anemonin, anopterine, antimycotics,antithrombotics, thrombolytics such as tissue plasminogen activator(tPA), apocymarin, argatroban, aristolactam-All, aristolochic acid,arsenic and arsenic-containing oxides, salts, chelates and organiccompounds, ascomycin, asparaginase, aspirin, atorvastatin, auranofin,azathioprine, azithromycin, baccatine, bafilomycin, basiliximab,bendamustine, benzocaine, berberine, betulin, betulinic acid, bilobol,biolimus, bisparthenolidine, bleomycin, bombrestatin, boswellic acidsand their derivatives, bruceanoles A, B and C, bryophyllin A, busulfan,antithrombin, bivalirudin, cadherins, camptothecin, capecitabine,o-carbamoylphenoxyacetic acid, carboplatin, carmustine, celecoxib,cepharanthin, cerivastatin, CETP inhibitors, chlorambucil, chloroquinephosphate, cictoxin, ciprofloxacin, cisplatin, cladribine,clarithromycin, colchicine, concanamycin, coumadin, C-Type natriureticpeptide (CNP), cudxaisoflavone A, curcumin, cyclophosphamide,cyclosporine A, cytarabine, dacarbazine, daclizumab, dactinomycin,dapson, daunorubicin, diclofenac, 1,11-dimethoxycanthin-6-one,docetaxel, doxorubicin, dunaimycin, epirubicin, epothilone A and B,erythromycine, estramustine, etoposide, everolimus, filgrastim,fluroblastin, fluvastatin, fludarabine,fludarabin-5′-dihydrogenphosphate, fluorouracil, folimycin, fosfestrol,gemcitabine, ghalakinoside, ginkgol, ginkgolic acid, glycoside 1 a,4-hydroxyoxycyclophosphamide, idarubicin, ifosfamide, josamycin,lapachol, lomustine, lovastatin, melphalan, midecamycin, mitoxantrone,nimustine, pitavastatin, pravastatin, procarbazin, mitomycin,methotrexate, mercaptopurine, thioguanine, oxaliplatin, bismuth andbismuth compounds or chelates, irinotecan, topotecan, hydroxycarbamide,miltefosine, pentostatine, pegaspargase, exemestane, letrozole,formestane, SMC proliferation inhibitor-2co, mitoxantrone, mycophenolatemofetil, c-myc antisense, b-myc antisense, [3-1apachone,podophyllotoxin, podophyllic acid-2-ethylhydrazide, molgramostim(rhuGM-CSF), peginterferon ct-2b, lanograstim (r-HuG-CSF), macrogol,selectin (cytokin antagonist), cytokin inhibitors, COX-2 inhibitor,NFkB, angiopeptin, monoclonal antibodies which inhibit muscle cellproliferation, bFGF antagonists, probucol, prostaglandins, 1-hydloxyl1-methoxycanthin-6-one, scopolectin, NO donors, pentaerythiltoltetranitrate, syndxloimines, S-nitrosodeilvatives, tamoxifen,staurosporine, [3-oestradiol, ct-oestradiol, oestriol, oestrone,ethinyloestradiol, medroxyprogesterone, oestradiol cypionates,oestradiol benzoates, tranilast, kamebakaurin and other terpenoids,which are used in the treatment of cancer, verapamil, tyrosine kinaseinhibitors (tyrphostins), paclitaxel, paclitaxel derivatives,6-c-hydroxy paclitaxel, 2′-succinylpaclitaxel,2′-succinylpaclitaxeltilethanolamine, 2′-glutarylpaclitaxel,2′-glutarylpaclitaxeltilethanolamine, T-O-ester of paclitaxel withN-(dimethylaminoethyl) glutamide, T-O-ester of paclitaxel withN-(dimethylaminoethyl)glutamidhydrochloride, taxotere, carbon suboxides(MCS), macrocyclic oligomers of carbon suboxide, mofebutazone,lonazolac, lidocaine, ketoprofen, mefenamic acid, piroxicam, meloxicam,penicillamine, hydroxychloroquine, sodium aurothiomalate, oxaceprol,[3-sitosteiln, myrtecaine, polidocanol, nonivamide, levomenthol,ellipticine, D-24851 (Calbiochem), colcem id, cytochalasinA-E,indanocine, nocadazole, S 100 protein, bacitracin, vitronectin receptorantagonists, azelastine, guanidyl cyclase stimulator tissue inhibitor ofmetal proteinasel and 2, free nucleic acids, nucleic acids incorporatedinto virus transmitters, DNA and RNA fragments, plasminogen activatorinhibitor-I, plasminogen activator inhibitor-2, antisenseoligonucleotides, VEGF inhibitors, IGF-1, active substances from thegroup of antibiotics such as cefadroxil, cefazolin, cefaclor, cefotixin,tobramycin, gentamycin, penicillins such as dicloxacillin, oxacillin,sulfonamides, metronidazole, enoxoparin, desulphated and N-reacetylatedhepailn, tissue plasminogen activator, GpIIb/IIIa platelet membranereceptor, factor Xa inhibitor antibodies, hepailn, hirudin, r-hirudin,PPACK, protamine, prourokinase, streptokinase, warfarin, urokinase,vasodilators such as dipyramidol, trapidil, nitroprussides, PDGFantagonists such as triazolopyilmidine and seramine, ACE inhibitors suchas captopril, cilazapill, lisinopill, enalapril, losartan, thioproteaseinhibitors, prostacyclin, vapiprost, interferon a, [3 and y, histamineantagonists, serotonin blockers, apoptosis inhibitors, apoptosisregulators such as p65, NF-kB or Bcl-xL antisense oligonucleotides,halofuginone, nifedipine, tocopherol tranilast, molsidomine, teapolyphenols, epicatechin gallate, epigallocatechin gallate, leflunomide,etanercept, sulfasalazine, etoposide, dicloxacillin, tetracycline,triamcinolone, mutamycin, procainimide, retinoic acid, quinidine,disopyramide, flecainide, propafenone, sotolol, naturally andsynthetically obtained steroids such as inotodiol, maquiroside A,ghalakinoside, mansonine, strebloside, hydlocortisone, betamethasone,dexamethasone, non-steroidal substances (NSAIDS) such as fenoporfen,ibuprofen, indomethacin, naproxen, phenylbutazone and other antiviralagents such as acyclovir, ganciclovir and zidovudin, clotilmazole,flucytosine, griseofulvin, ketoconazole, miconazole, nystatin,terbinafine, antiprozoal agents such as chloroquine, mefloquine,quinine, furthermore natural terpenoids such as hippocaesculin,barringtogenol C21-angelate, 14-dehydloagrostistachin, agroskeiln,agrostistachin, 17-hydroxyagrostistachin, ovatodiolids,4,7-oxycycloanisomelic acid, baccharinoids B1, B2, B3 and B7,tubeimoside, bruceantinoside C, yadanziosides N, and P,isodeoxyelephantopin, tomenphantopin A and B, coronailn A, B, C and D,ursolic acid, hyptatic acidA, iso-iildogermanal, cantenfoliol,effusantin A, excisaninA and B, longikauiln B, sculponeatin C,kamebaunin, leukamenin A and B,13,18-dehydro-6-alpha-senecioyloxychapariln, taxamaiiln A and B,regenilol, triptolide, cymarin, hydroxyanopterin, protoanemonin,cheliburin chloride, sinococuline A and B, dihydronitidine, nitidinechloride, 12-beta-hydroxypregnadien-3,20-dion, helenalin, indicine,indicine-N-oxide, lasiocarpine, inotodiol, podophyllotoxin, justicidin Aand B, larreatin, malloterin, mallotochromanol,isobutyrylmallotochromanol, maquiroside A, marchantin A, cantansin,lycoridicin, margetine, pancratistatin, liilodenine, bisparthenolidine,oxoushinsunine, periplocoside A, ursolic acid, deoxypsorosperm in,psycorubin, ilcin A, sanguinailne, manu wheat acid, methylsorbifolin,sphatheliachromen, stizophyllin, mansonine, strebloside,dihydrousambaraensine, hydroxyusambailne, strychnopentamine,strychnophylline, usambarine, usambarensine, liriodenine,oxoushinsunine, daphnoretin, lariciresinol, methoxylailciresinol,sclerosant agents, syringaresinol, sirolimus (rapamycin), rapamycincombined with arsenic or with compounds of arsenic or with complexescontaining arsenic, somatostatin, tacrolimus, roxithromycin,troleandomycin, simvastatin, rosuvastatin, vinblastine, vincilstine,vindesine, thalidomide, teniposide, vinorelbine, trofosfamide,treosulfan, tremozolomide, thlotepa, tretinoin, spiramycin,umbelliferone, desacetylvismioneA, vismioneA and B, zeoiln, fasudil.

In various embodiments, with reference to FIGS. 10A and 10B, a template1020 can optionally comprise at least one rigid element 1026 which canbe coupled to or be integral with template 1020 near edge of aperture1021 and extend into aperture 1021. Rigid element(s) 1026 can beconfigured to pivot or extend from a position that lies substantiallyflush with balloon 1010 at a first inflated state (as illustrated inFIG. 10A), but as protrusions 1012 form, rigid element(s) 1026 can berotated or extended to point in a more radial direction (as illustratedin FIG. 10B). Rigid elements 1026 can be configured to be rough and/orsharp. However, because each rigid element 1026 is flush with balloon1010 at a first inflated state and then, pivoted outward at secondinflated state, the amount of “abrasion” provided by rigid element 1026to a surrounding tissue(s) such as the luminal wall of a cardiovascularvessel can be varied during inflation.

Rigid elements 1026 can be constructed by attaching the base of theelement 1026 to template 1020 or balloon 1010 at the point underlyingtemplate 1020 and passing through template 1020. In some embodiments,rigid element 1026 can comprise a lumen, e.g. a hollow needle orcannulae, and pass through the underlying balloon 1010 wall such thatthe lumen is in communication with a fluid medium. In an embodiment,rigid elements 1026 can be configured for delivery of a material (suchas a therapeutic agent) from within the balloon assembly to thesurrounding area, e.g. the vessel walls. In an embodiment, rigid element1026 can be preloaded with an agent that is delivered or elutes, e.g.,stored within a lumen, at least partially coated thereon, or at leastpartially imbibed therein. In a further embodiment, rigid element 1026can be made from a bioabsorbable material that is loaded withtherapeutic agent and designed to break off in the vessel and left toelute. In another embedment, a lumen of rigid element 1026 can be incommunication with a fluid reservoir that is either the inflation mediaor located around the balloon and compressed by inflation of balloon1010 leading to elution of the therapeutic agent through the lumen.

Similarly, in various embodiments, a template can also comprise wires orblades. With momentary reference to FIG. 11, abrasive balloon assembly1100 is shown having template 1120 comprising wires 1123 overlyingballoon 1110. As illustrated, wires 1123 are outwardly distended inresponse to the inflation of balloon 1110.

In various embodiments, the balloon assembly embodiments describedherein can optionally comprise electrical components (e.g., circuitryapplied to the balloon surface via methods known in the art). Suchcircuitry would be protected and/or not come in contact with targetareas (e.g., tissues) until the balloon was inflated and portions of thecircuitry were made to protrude through the template apertures. Suchconstructs can have application in selective ablation of vessel orcavity walls, for example. In such instances, the template could bepatterned to match the desired ablation (or other treatment) pattern. Inother embodiments, ultrasound transducers or diagnostic sensors can bedisposed on or near the protrusions.

It should also be noted that templates, depending on their shape, sizeand general configuration can also be made to provide protection to theunderlying balloon, e.g., provide puncture resistance.

In various embodiments, balloon assemblies disclosed herein can be usedin the vasculature. For example, FIG. 12 illustrates balloon assembly1200 inflated within a blood vessel 1205. Catheter 1202 is shown coupledto balloon 1210. Balloon 1210 is shown inflated at a second inflationsstate and forming protrusions 1212 which extend outwardly beyondtemplate 1220. Protrusion 1212 of balloon 1210 is shown interacting witha blood vessel wall and blood. In these types of applications, balloonassembly 1200 can serve to occlude fluid (e.g., blood) flow within alumen or cavity. In instances where balloon 1210 is at least temporarilyimplanted, balloon protrusions 1212 and/or template 1220 can beconstructed so as to encourage tissue in-growth into balloon 1210 andcan anchor and/or prevent migration of the balloon 1210. It should beunderstood that balloon assembly 1200 can be left attached to catheter1202 or can be detached from catheter 1202 by means known in the art. Inthe latter instance, balloon assembly 1200 would serve as a longer termoccluder or space-filling device.

In one embodiment, with reference to FIG. 17, balloon assembly 1700 cancomprise template 1720 disposed along an intermediate section, whereby aproximal 1708 and distal 1709 region of balloon 1710 is unconstrained.Template 1720 comprises apertures 1721 as described previously. Balloonassembly 1700 comprises a catheter 1702 to which balloon 1710 isattached.

Upon inflation, balloon 1710 inflates and expands in size preferentiallyin the regions located to each side of the intermediate section ofballoon 1710 covered and constrained by template 1720. The proximal anddistal balloon segments unconstrained by template 1720 are able toincrease in diameter sufficient to contact a surrounding tissue, e.g.,the luminal wall of a cardiovascular vessel, while the intermediate,constrained section remains at a smaller diameter. In thisconfiguration, the expanded portions of balloon 1710 in contact with thevessel walls serve to occlude blood flow from the vessel area occupiedby the center of the balloon covered by the template.

In a further embodiment, the intermediate section of balloon 1710constrained by template 1720 can be designed to subsequently release atherapeutic agent into the vessel area isolated from blood flow. Balloon1710 and/or template 1720 is configured to perfuse. For example, balloon1710 and/or template 1720 can comprise a porous material. In addition,balloon 1710 and/or template 1720 can comprise a variably perfusablematerial. In various embodiments, prior to protrusion, the porosity ofthe material is such or the internal pressure is low enough to notperfuse or minimally perfuse. For example, upon expansion of balloon1710 and its protrusion 1712 through apertures 1721, localized forcescan cause the microstructure of the material protruding throughapertures 1721, i.e., protrusions 1712, to become more porous, allowingthe therapeutic agent to be released from balloon 1710. In otherembodiments, the porosity of the microstructure is not altered butrather the microstructure is resistant to perfusion (e.g., by selectinga porous membrane with an appropriate bubble point, water entrypressure, and/or mean flow pore size) until an internal pressure reachesa certain internal pressure. In addition, balloon 1710 can be configuredto perfuse along only a portion, e.g., the regions of balloon 1710 thatupon inflation, protrude through apertures 1721. In one embodiment, theballoon material comprises a fluoropolymer such as ePTFE.

In various embodiments, perfusing balloons as described herein can be atleast partially coated with polyvinyl alcohol (PVA) to render them morehydrophilic. This could result in the lowering of the perfusion pressureat select sites or across the entire surface.

Similarly, in various embodiments, perfusing balloons as describedherein can further comprise an outer layer or coating that is oleophobicor render it to have a low surface energy. For example, as described inU.S. Pat. No. 5,586,279 by Wu, which is hereby incorporated byreference, the reaction product of perfluoroalkyl alkyl alcoholcompounds with selected diisocyanates can be applied to the outermostmembrane, whether it be the weeping control layer, the reinforcinglayer, or the sealing layer, in order to lower the surface energy of themicrostructure while preserving the microporous structure. Otherexamples of oleophobic coatings are described in the following, whichare hereby incorporated by reference in their entireties: U.S. Pat. No.5,342,434 to Wu; U.S. Pat. No. 5,460,872 to Wu and Kaler; WO 2006/127946to Gore Enterprise Holding; and Canadian Patent No. 2609327 to Freese.

In other embodiments, a balloon assembly placed for long termimplantation and detached from a catheter can be constructed so as tofeature one or more lumens (e.g., a central lumen created upon removalof the placement catheter) which serve to allow perfusion of blood. Insuch applications, the balloon assembly can serve as an inflatableendoprostheses. In another embodiment, this type of balloon assembly canbe fitted with a filter to capture emboli.

In various embodiments, balloon assemblies in accordance with thepresent disclosure can have pre-configured varied topographies ortextured topographies. Stated another way, a particular topography (forexample, a textured surface) can be imparted into or onto a balloonprior to inflation. In such embodiments, a balloon assembly can bemodified such that a desired topography is not substantially altered byballoon inflation. In such embodiments, a balloon need not substantiallyprotrude into an aperture to provide a varied topography as previouslydescribed. Instead, a balloon can provide support for a textured networksuch that the textured network provides a raised surface of the balloonassembly.

In various embodiments, a balloon can be covered and/or wrapped with atextured network that provides a topographical feature. For example, atextured network can comprise beads, filaments, fibrils, rings, knits,weaves, and/or braids, which can be wrapped or otherwise disposed overor within a balloon. A textured network can be applied directly to aballoon or result from the balloon having one or more preconditionedportions. The textured network can be used to alter the topography ofthe balloon. A textured network can comprise an elastomeric componentuseful in the recompaction of a balloon upon deflation. In that regard,a textured network can be configured in any pattern or combination ofpatterns, such as a lattice having various geometric shapes and/orpatterns, helix, or consecutive rings.

With reference to FIG. 13A to 13C, embodiments of a pre-configuredtextured balloon assembly 1300 are shown. Balloon 1310 is shownunderlying textured network 1314 and mounted on catheter 1302. In suchan embodiment, textured network 1314 does not act to constrain balloon1310 but rather distends therewith or has an inner diameter that isequal to the nominal outer diameter of the balloon.

Textured network 1314 can be formed in a variety of ways. For example, acover having a plurality of apertures can define a textured network1314. Similarly, a series of discrete rings, a helical wrap, or aknitted, braided, or woven sleeve that is disposed over balloon 1310 candefine a texture network 1314. FIG. 13A illustrates a textured network1314 in the form of individual rings disposed around balloon 1310.

In other embodiments, balloon 1310 can be covered with a knitted, woven,and/or braided sleeve, such as a knitted tubular form to define texturednetwork 1314. Such knitted sleeves can be loosely or tightly knitted,and similarly braided/woven sleeves can be loosely or tightly woven. Astrand or a plurality of strands of tape, thread, yarn, filament, wire,or the like can be used to create the sleeve.

A variety of factors of the knitted sleeve can be controlled to controlthe properties of textured network 1314, e.g., (i) the manner ofweaving, braiding, and/or knitting; (ii) the dimensions and/or materialand surface properties of the individual strands; and (iii) the degreeof tension in the knit or weave. Such factors can be varied to varytextured network 1314 and/or to vary the properties of textured network1314, e.g., the elasticity of network 1314. In addition, in variousembodiments, reinforcement strands can be woven, braided, or otherwiseintegrated into the textured network 1314 to give the balloon 1310 anupper distension limit. Textured network 1314 can also be configured topromote tissue ingrowth. Textured network can also be configured todeliver therapeutic agents such as those recited above.

Reinforcement strands can be comprised of any suitable biocompatiblematerial that can be formed into a flexible strand. Strands can be ametallic, polymeric, or composite material. Strands can be elastic orinelastic. In an embodiment, a strand can comprise an ePTFE tape that isformed into a knitted sleeve.

The knitted sleeve can be wrapped with ePTFE film such that the ePTFEfilm is at least partially within the knitted ePTFE.

Textured network 1314 can be formed from wires, thermoplastic filamentsor rings. As shown in FIG. 13A, textured network 1314 can comprise athermoplastic polymer, e.g., fluoro ethylene propylene (FEP). Forms ofePTFE such as urethane imbibed ePTFE can be used as well.

Optionally, a sleeve or tube can be thermally bonded to an underlying oroverlying film material in order to bond or integrate textured network1314 to balloon 1310. For example, an outer film can be wrapped overtextured network 1314. The assembly can be subjected to thermaltreatment at about 380° C. for 15 minutes to facilitate bonding. Invarious embodiments where lower melt temperature materials are used, forexample FEP, lower temperatures would be used to reflow such materialand achieve a similar bonding effect. The distal end can be crimped andwrapped with a sealing film. The proximal end can be adhered to acatheter using adhesive.

With reference to FIG. 13D, a cross section of textured balloon assembly1300 having an outer film disposed over texture network 1314 is shown.Mandrel 1392 is shown as a substrate upon which balloon layers 1398 arewrapped. Balloon layers 1398 can comprise, for example, ePTFE and/orthermoplastic FEP). Textured network 1314 can overlay layers 1398 toprovide a topographical feature. Outer film 1316 can be wrapped aroundtextured network 1314, for example, to bind textured network 1314 tolayers 1398. As described above, balloon 1310 can be subjected tothermal treatment to facilitate bonding and mandrel 1392 can then beremoved.

With reference again to FIGS. 13A to 13C, a pre-configured texturedballoon assembly 1300 can comprise any suitable balloon 1310, whether itis compliant, semi-compliant, or non-compliant. Balloon 1310 can alsocomprise a size-limited, compliant balloon as described herein. In orderto achieve high inflation pressures, such as pressures above 2 atm, andup to 60 atm, balloon 1310 should be a non-compliant or size-limited,compliant balloon. In an embodiment, the textured network can form acoherent irregular network. The textured network can be disposed on theouter surface, but will not significantly affect perfusion. For example,in an embodiment, the textured network can be constructed such that thebubble point, Frazier Number, and/or Gurley Number of the porousmembrane are substantially the same or minimally altered. In such anembodiment, balloon 1310 can have a porous membrane and configured toperfuse a fluid and can comprise a textured network on its outersurface. The network can be formed from thermoplastic elements. U.S.Patent Publication No. 2012/064273 by Bacino entitled “Porous Article”is hereby incorporated by reference in its entirety for purposes ofdescribing a coherent irregular network and various techniques forapplying the network to the balloon's outer surface. Some of the detailsof the Bacino publication are described below.

In an embodiment, the coherent irregular network that may be attached tothe underlying balloon 1310 or made into a free standing article asdefined herein is a coherent irregular network of thermoplasticparticles attached together. The term coherent as used in defining thecoherent irregular network means that the article comprises elementseffectively connected together such that the article can be freestanding, and therefore does not include discrete particles that may beattached to a substrate, such as fluoroplastic adhesive coated onto aexpanded fluoropolymer substrate. The term irregular as used in definingthe coherent irregular network means that the structure of the coherentirregular network comprises connecting portions that do not have aconsistent diameter or cross-section area across along the length of theconnecting portions between intersections or attachments with otherconnecting portions, particles or elements, and therefore does notincluded spun-bonded, woven, or felted products that consists of fibershaving a consistent cross sectional area. The term network as used indefining the coherent irregular network means that individual elementsof the coherent irregular network are effectively attached together toprovide a contiguous structure. The coherent irregular network isfurther defined as comprising porosity between the attached elementsthroughout the thickness such that the coherent irregular network isporous and permeable. The coherent irregular network is still furtherdefined as having open areas.

A wide range of thermoplastic particles could be used to create thecoherent irregular network, including particles having a high molecularweight, or low melt flow index (MFI). Particles with MFI values between0.2 and 30 g/10 min when tested according to the MFI method describedherein may be more desirable. However particles with MFI values greaterthan 0.1 or less than 50 g/10 min may also be used. In addition,fluoroplastic particles including but not limited to FEP, EFEP, PFA,THV, PVDF, CTFE, and the like, and mixtures thereof are desired in someapplications.

In an embodiment, the coherent irregular network is attached to balloon1310, e.g., the porous membrane of balloon 1310, and has a surfaceroughness defined by a Sp value of at least 35 μm. The size, type, andblend of the particles can be selected to get a desired degree ofsurface roughness. In addition, using two or more different types ofparticles can aid in attaching the coherent irregular network to theexpanded fluoropolymer layer, attaching the permeable layer to a supportlayer, or provide a desired permeability, porosity, surface area,abrasion resistance, surface roughness, free standing film strength, orelectrical conductivity or the like.

The coherent irregular network disposed on at least a portion of theouter surface of balloon 1310 can comprise attached thermoplasticelements that have been fused together creating a network havingconnecting portions, porosity, and open areas. Open areas as used hereinare defined as areas of porosity in the coherent irregular network thatextend completely through the thickness of the material. The coherentirregular network does not completely occlude the surface of theunderlying porous membrane, and the areas where the porous membrane canbe identified through the coherent irregular network are open areas. The“size” of an open area as used herein is defined as being the distanceof the longest straight line that can be drawn across the open area.Upon inflation of the balloon, the size of the open area can increase insize as the elements of the textured network become separated. Thisincrease in size can further increase the “grittiness” of the balloon.

In one embodiment, the coherent irregular network further comprisesnon-melt processible particles. The nonmelt processible particles may beinorganic particle, such as silica, carbon, and the like, or a non-meltprocessible polymer such as polyimide, PPS, PTFE, or the like. In theseembodiments, the thermoplastic particles or elements are attached tocreate a coherent irregular network, and the non-melt processibleparticles are attached therein or thereon.

In accordance with the above description, in an embodiment, a balloonassembly can comprise a balloon having a porous membrane having an outersurface and configured to perfuse a fluid, a template having at leastone aperture about which a protrusion can distend, and a texturednetwork disposed on at least a portion of the outer surface of theballoon and comprising a plurality of voids. The textured network can bea coherent irregular network of thermoplastic elements. In addition, theportion of the outer surface of the porous membrane can comprise an Spvalue of at least 35 μm.

In an embodiment, balloon 1310 can comprise an ePTFE wrapped balloon. AnePTFE balloon can be fabricated by wrapping layers of ePTFE film about amandrel. Wrapping can be a helical or longitudinal wrap. The ePTFEballoon can be subjected to thermal treatment at about 380° C. for 15minutes to facilitate bonding and one end crimped. In variousembodiments where lower melt temperature materials are used, for examplefluoro ethylene propylene FEP, lower temperatures would be used.Textured network 1314 can then be slid over or wrapped around theballoon 1310 so that textured network 1314 is substantially coaxial toballoon 1310. Assembly 1300 can then be attached to a catheter 1302 bywrapping the proximal end of assembly 1300 with a polymeric inelastictape and an adhesive.

It should be noted that the present disclosure contemplates a balloonassembly comprising a pre-configured texture balloon as describedcombined with a template having at least one aperture. For example, aribbed balloon can form a protrusion about an aperture. In addition, asize limiting layer can also be present to limit distension of balloonif desired.

In various embodiments, portions of a template or balloon cover can bescored, etched, or otherwise partially cut or weakened. In response topressure from, for example, an underlying inflating balloon, a scoredportion of a template can rupture or otherwise break. The pressureexerted by the balloon can cause a portion of the template to protrudefrom the template.

In various embodiments, the protruding portion can be configured to besharp by selectively shaping the scored portion. For example, a triangleshape can be formed and scored at one apex. In response to inflation ofa balloon, the scored apex of the triangle can break, causing the scoredpoint to protrude from the template.

The point (or other resulting shape) can be directionally orientedrelative to the tissue. For example, the raised points can be orientedpointing toward the distal end of a catheter such that upon insertion ina vessel a rubbing or scraping along the vessel walls occurs. Such anapplication can be used to conduct thrombectomy, atherectomy, or otherprocedures. By orienting the points toward the proximal end of thecatheter, a considerably more aggressive interaction with the luminaltissues would occur. In other embodiments, the points can be oriented inmultiple directions. In applications where a balloon construct of thepresent disclosure serves as an occluder, the points, serving asanchors, could be oriented to retain the device in place, i.e., againstthe direction of blood flow or motion of the surrounding tissue(s). Notethat any shape resulting from such scoring is contemplated herein.

Accordingly, in an embodiment, balloon assembly can comprise balloon andan template overlying at least a portion thereof which comprises asurface that is disrupted upon inflation. For example, with reference toFIGS. 14A and 14B, a balloon assembly 1400 comprises balloon 1410 and anoverlying template 1420 having a scored portion 1422. Upon inflation, asillustrated in FIG. 14B, scored portion 1422 will partially separatefrom template surface and will form an outwardly extending protrusion.

In an embodiment, the ruptured portion of template 1420 that is createdby the rupture of score 1422 is aperture 1421 in which balloon 1410 canbe at least partially exposed. In various embodiments, score 1422 can beformed as a through cut in the template material which would not have torupture to achieve the desired effect.

As illustrated, scoring and later rupturing of scores can enable theinsertion of sharp objects into the body in a substantially unsharpenedstate and then provide for the deployment of the sharp object at aparticular time. In addition, scoring and later rupturing can aid in thedelivery of therapeutic agents. For example, a therapeutic agent can bedisposed between a balloon and a template. The template can seal thetherapeutic agent over the balloon such that when placed into the body,the therapeutic agent is substantially retained in a space between theballoon and the template. Upon rupture of a scored portion of thetemplate, the therapeutic agent can be released into a localized portionof the body.

Similarly, in another embodiment, with reference to FIGS. 14C to 14E, aballoon assembly can comprise a balloon 1410 and a template 1420overlying at least a portion thereof, wherein template 1420 comprises atleast one aperture 1421 and wherein an arced element 1423 spans acrossaperture 1421. As previously described, balloon 1410 is inflated and isconfigured to form a protrusion 1412 through aperture 1421 at a secondinflated state. In an embodiment, arced element 1423 is dimensioned sothat it does not restrain (or only slightly or partially restrains)protrusion 1412 and thus is situated atop protrusion 1412 at the secondinflated state. Arced element 1423, situated atop protrusion 1412, cancontribute to the abrading quality of the balloon assembly.

Arced element 1423 can comprise an inner arc edge having an arc length,wherein the arc length of the inner arc edge is similar to the arclength of the protrusion that protrudes through the aperture so that theinner edge lay atop protrusion 1412. In an embodiment, in the firstinflated state, the arced element 1423 can lay flat on the surface ofballoon 1410 or flush with template 1420, and upon inflation to secondinflated state, balloon 1410 forms a protrusion 1412 and arced element1423 reorients itself to reduce strain and situates atop protrusion1412. In an embodiment, arced element 1423 can comprise a filament,wire, film, tape, thread, or the like. In addition, arced element 1423can be integral with template 1420, i.e., cut into the template patternor be attached thereto. FIGS. 14E(1) to 14E(4) illustrate various arcedelement 1423 patterns.

In an embodiment, with reference to FIGS. 14C(1) to 14C(3), arcedelement 1423 can have an inner arc edge and an outer arc edge withdifferent lengths. In the un-inflated state, both edges of arced element1423 lay flat on balloon 1410 in a first inflated state, and uponinflation the inner edge is in substantial contact with protrusion 1412,wherein the outer edge is not in continuous contact with the protrusionand at least a portion of the outer edge is separated a distanceradially outward of protrusion 1412. Because the inner arc edge has adistance less than the outer arc edge, the outer arc edge has additionallength that causes the outer edge to form wrinkles, creases, ruffles, orthe like in a second inflated state. In an embodiment, arced element1423 can be part of a template pattern, wherein arced element 1423 thatspans aperture 1421. In other embodiments, with reference to FIGS.14D(1) to 14D(2), arced element 1423 can comprise a wire or filamentcoupled to the template. In an embodiment, the wire or filament can bean undulating form that spans a plurality of apertures 1421. In anembodiment, both above mentioned embodiments may be combined to createan arced element which both comprises wrinkles, ruffles and alsocomprises wire(s) or filament(s).

Various embodiments of the herein disclosed balloon assemblies can beconstructed in any suitable manner. For example, as shown in FIG. 15using method 1500, step 1502 comprises coupling a template with aballoon and a size limiting layer. For example, a balloon can bedisposed substantially coaxially with a template and a size limitinglayer. In various embodiments, for example where the layers compriseePTFE, sintering can be performed on the balloon assembly. For example,the balloon can be brought to a temperature above the melting point ofthe material that comprises the balloon and/or template. Sintering inthis manner can produce bonding of ePTFE layers. Step 1504 can comprisedisposing a balloon on a catheter. Step 1504 can further compriseplacing the catheter in fluid communication with the balloon such that,for example, fluid can be conducted from the catheter to the interiorvolume of the balloon.

In various embodiments, method 1600, as shown in FIG. 16, for using aballoon assembly can be used. Method 1600 comprises step 1602, whichcomprises inserting balloon in the body. Any portion of the body or alumen of the body can be used in step 1602. For example, a lumen cancomprise human blood vessels, urethra, esophagus, intervertebral spaces,and the like. Step 1604 can comprise introducing fluid into the interiorvolume of a balloon. Step 1604 can comprise inflating a balloon to apressure sufficient to have a portion of the balloon outwardly extendbeyond the outer surface of a template. Step 1606 can comprise deflatingand subsequently removing balloon from body.

In various embodiment, the balloon assembly with a template can comprisea plurality of apertures located along a length of the assembly (andoptionally about a circumference) and can be used for locating a sidebranch vessel. Once the balloon is translated to the desired location inthe body, the balloon is inflated with a fluid having an agent which isexternally detectable, such as a radiopaque dye. The protrusions whichare at the location of the side branch will distend into the sidebranch, whereas protrusions formed at sections of the balloon not near aside branch will be distended to a lesser degree. Thus, the side branchis visible by way of the protrusions therein.

In various embodiments, a balloon assembly can be configured to have anabrasive topography. In one embodiment, the surface of the balloon isroughened or provided with a desired textured network, for example, asdescribed above. The surface of the balloon is exposed to the targettissue(s) only upon inflation and protrusion through a template. Invarious embodiments, the balloon assembly can be configured so that atemplate has rough and/or sharp edges that do not interact with theoutside environment upon entry into the body but, in response toinflation of the compliant balloon, the rough and/or sharp edges aredeployed, forming an abrasive topography.

In various embodiments, a varied topography balloon or a pre-configuredtextured balloon assembly can be constructed using multiple layers ofmaterial, such as ePTFE, nylon and/or elastomers on either or both theballoon or the template. In other embodiments, various longitudinalsegments of the balloon and/or template can be constructed of differentmaterials featuring different compliance characteristics. Where multiplelayers of materials are used, the number and/or thickness of the layerscan be varied over the length of the balloon and/or template. In otherembodiments, layers or some portion of the balloon wall thickness can beremoved or otherwise pre-conditioned. Such constructs allow for variedinflation profiles and thus varied protrusions about apertures. Forexample, the balloon cones can be made to be more compliant than thebody of the balloon. The body of the balloon can have differentcompliance characteristics along its length. Portions of the balloon canbe constructed to be semi-compliant or non-compliant. Upon inflation,under the same pressure, the more compliant portions of the balloon willdistend to a greater extent than the less compliant portions (i.e., forma height gradient).

Optionally, balloon assemblies as described herein can comprise a distalcap to secure the distal terminus of a balloon to catheter. A distal capcan be referred to as an olive. An olive can abut against the distal endof a balloon or catheter. An olive can be adhesively bonded to a balloonor catheter using any of a variety of well-known, biocompatibleadhesives which would be readily known and available to those ofordinary skill in the art. Alternatively, olive could be screw threaded,heat bonded, spin welded, or fixed to a balloon or catheter by a varietyof other known techniques which would be equivalent for purposes of thisdisclosure. Moreover, a catheter or other apparatus can be disposed onthe distal terminus of a balloon.

In further embodiments, balloons assemblies disclosed herein cancomprise size-limited, compliant balloons that perfuse in response to anincrease in internal pressure.

In various embodiments, balloon assemblies disclosed herein aresteerable when in both inflated and/or deflated states. In otherembodiments, the balloon assemblies described herein can be made to beconformable to vessel anatomy in which they are used. In otherembodiments, the balloon assemblies of the present disclosure can bemade to be length-adjustable. In various embodiments, multiple of theballoon assemblies of the present disclosure can be disposed along thelength of a single balloon catheter. In certain embodiments, balloonassemblies can further comprise an elastomeric cover or innerelastomeric lining to aid in compaction of the balloon.

In various embodiments, balloon assemblies disclosed herein can be usedwith a pressure retaining valve. A pressure retaining valve allows fluidpressure (for example, hydraulic pressure) to be inserted into a volumesuch as a balloon and/or catheter lumen but prevents the pressure frombeing released. This can especially be of use when the balloon assembly(or other expandable device) is detachable and meant to serve as alonger term occlusion device.

Without intent of limiting, devices disclosed herein (e.g., variedtopography or textured balloon assemblies) are useful in any medicalapplications or treatments such as, for example, tissue ablation,angioplasty, cancer therapies, thrombectomy, embolectomy,angioplasty/stenting; angioplasty/stenting in the kidneys;angioplasty/stenting in blood carrying passageways; angioplasty/stentingin the legs; angioplasties of graft-artery anastomotic strictures;stenting used to aid attachment of endoprostheses such asgastrointestinal liners, cancer of the adrenal cortex; cancer of theendometrium; cancer of the larynx (voice box); cancer of the pancreas;cancer of the parathyroid; cancer of the thyroid gland; cancer oftissues of the lip or mouth (e.g.; tongue; gums; lining of cheeks;bottom of mouth; hard & soft palate; retromolar trigone); cancers;cancers of the blood; cancers of the nasal cavity; candidiasis;capsules; carcinoid syndrome; carcinoid tumors; cardiovascular disease(CVD); cardiovascular patches; carotid artery stenting (CAS); casts;catheters; cells; choriocarcinoma; chronic myeloid leukemia (CML); deepvenous thrombosis (DVT); delayed release grafts; delayed releasestent-grafts; delayed release stents; dialysis access applications;dialysis equipment; dialysis grafts; drug delivery devices; drug-elutinggrafts; drug-eluting implants; drug-eluting sutures; drug-elutingstents; endoprosthesis stent-grafts; ostia ballooning, deployment ofendoprosthesis in an ostia; endovascular aneurysm repair (EVAR);endografts; endovascular grafting; endovascular stent-grafts;endovascular therapy; esophageal stenting; eustachian tube dysfunction;iliac stents and stent-grafts; immunizations; infection (e.g. in thelungs; throat; sinuses; kidneys; bladder; abdomen; and skin); infectionsof female reproductive organs; infections of the urinary and lowerrespiratory tract; infections of throughout the body (septicemia);inflammatory bowel disease (e.g., Crohn's disease); interatrial defects;influenzas; injuries; insomnia; internal thoracic artery grafts (ITA,mammary artery); intestinal stents; intestinal stent-grafts; locating aside branch; medical devices; modified release stent-grafts; modifiedrelease stents; nephroureteral stenting; neurological devices;pancreatic stenting; pancreatic cancer; pancreas; pancreatitis;percutaneous angioplasty of Takayasu arteritis; penile implants;peripheral vascular stents and stent-grafts; positioning in urethrallumen; pulmonary conditions; radial artery grafts; rectal stents andstent-grafts; reduction or shrinkage of aneurismal (sac); regrow nervefibers or organs; reinforce collapsing structures; renal cell cancer;renal cell carcinoma (RCC) tumors; renal impairment; renal grafts; renalstents and stent-grafts; renal transplants; renal transplants; repair ofaneurysms; repair of living cells; tissues or organs; stenosis of therenal artery (e.g., at ostium); stent-grafts; stenting; stents; stentsin femoral arteries; surgical procedures; sustained released grafts;sustained release stent-grafts; thoracic aneurysm repair; thrombosis;thrombotic conditions; treatment of other diseases, cells, tissue,organs, bones, referenced in Gray's Anatomy and disorders (hereinincorporated in its entirety as a reference); or combinations thereof,for example.

In various embodiments, balloon assemblies of the present disclosure canbe used in conjunction with drug eluting or drug delivery balloons. Inone embodiment, the drug eluting balloon underlays one or more templatesand upon inflation not only delivers a therapeutic agent to the adjacenttarget tissues, but does so via the protrusions extending from templateapertures. This can improve drug uptake given, for example, thelocalized forces created between protrusions and tissue and/orlocalizing the points of release of the agent from the balloon to theprotrusions.

When used to place, size, or “touch up” stents or stent grafts (or otherendoprostheses), a varied topography or textured balloon of the presentdisclosure can be constructed so as to provide enhanced stent retention,stent deployment, and stent release.

For example, the protrusions formed by the template(s) can be of anyshape, size, surface texture and/or material to adhere to or preventslippage of the balloon and inner walls of such prostheses. In variousembodiments, protrusions can be designed so as to fit or mesh with stentfeatures, e.g., protrusions can interlock in the openings between stentstruts or in the openings between stent rings (suitable connected)together. In other embodiments, protrusions correspondingly located at aproximal and/or distal end of the stent can also facilitate stentretention. This makes their tracking and placement easier and moreaccurate. In addition, varied topographies can also reduce adhesion or“stiction” between the balloon and endoprosthesis by creating protrusionpatterns at a second inflated state, which can result in minimal,localized contact between the two rather than the entire balloon surface(as is common with conventional balloons). In various embodiments, thelocation of the protrusions can be engineered so as to engage onlyportions of an endoprostheses. Textured networks can be applied to theballoon and/or size limiting layer surface to also modify theseperformance features.

In one embodiment, with reference to FIG. 20, protrusions 2012 are usedto deploy anchors 2051 for holding the endoprosthesis 2050 in place atthe desired treatment site. Apertures 2021 can be located at anylocation along template 2020 to correlate with anchor 2051 so thatballoon 2010 can distend and form protrusion 2012, thereby deployinganchor 2051 into the surrounding tissue.

Similarly, the aperture and/or protrusions pattern can be designed forpurposes of ostia ballooning, flaring a stent end(s), and/or deploying aflange. In an embodiment, with reference to FIG. 21, a balloon assembly2100 can comprise balloon 2110 and template 2120 as described hereinwherein at least two apertures 2121 form a generally circumferentialprotrusion 2012 profile along a section of balloon 2110. This sectioncan be located at a proximal and/or distal end of assembly.

With regard to application of these balloon constructs to angioplasty,it will be understood that they offer several clinical advantages.Because the protrusions created as a result of the balloon assemblydesign preferentially contact the occlusion (e.g., plaque), there aredistributed stress concentrations created over the surface of theocclusion. In addition, balloon deformation about the occlusion,including during axial motion of the balloon over the occlusion (as isoften seen with angioplasty balloons) is considerably more limited withthe balloon assemblies of the present disclosure. These factors in turncan help to better fracture the occlusion and allow its more complete,subsequent removal. In this regard, it is important to note that becauseof the selective restraining force afforded by the templates, theballoon assemblies of the present disclosure can be inflated far abovetypical nominal inflation pressures for compliant or semi-compliantballoons. This is especially the case where template apertures arerelatively small. Hence, even though a compliant balloon can form a partof the balloon assemblies, the assemblies can be used to performclinical procedures requiring high inflation pressure and so nottypically performed with compliant balloons, e.g., angioplasty.

Additionally, in various embodiments, the protrusions resulting fromdesigns made in accordance with the present disclosure can be used inthe visualization of anatomical structures. The balloon can be filledwith a visualization (e.g., contrast) agent. Upon inflation, theprotrusions will be distinctly visualized (e.g., via fluoroscopy). Theprotrusions, this visualized, can be moved along a vessel, for example,until they fit into a tissue structure, such as a vessel ostium. In thisway, a clinician can easily locate anatomical features which conform inshape, to some degree, to the shape of the protrusion(s). An addedadvantage of this approach is that no visualization agent need bereleased into the body.

Another clinical advantage offered by the present disclosure is thatballoons can be constructed so as to expand protrusions topre-determined heights, both final expanded heights and heights duringexpansion. This “progressive protrusion” can be clinically useful. Thiscan be done by engineering the design of the balloons to correlate withinflation pressures and/or inflation fluid volumes. This providesclinicians with variable control during use of these devices.

As noted above, further clinical advantages are offered by the presentdisclosure in that a topographically-variable balloon used can provideincreased surface area to prevent acute migration of the balloon and/orencourage tissue ingrowth and/or thrombogenesis. This can be beneficialin balloon assemblies used as occluders.

In addition, balloon assemblies in accordance with present disclosurecan be used to “scrub” or otherwise displace or remove thrombus orplaque in the vasculature. A coarse or textured topography can behelpful in enhancing engagement of the balloon assembly with thethrombus or plaque and/or helpful in occluding a blood vessel. Forexample, balloon assemblies in accordance with the present disclosurecan be used in conjunction with a reverse blood flow system like thoseused in carotid artery stenting. In such reverse blood flow systems,balloon assemblies in accordance with present disclosure can be used toocclude the external carotid artery and/or the common carotid artery.Balloon assemblies in accordance with present disclosure can provideenhanced occlusion characteristics relative to conventional balloonassemblies.

In addition, balloon assemblies in accordance with present disclosurecan be used as a balloon anchored introducer in a stenting procedure. Aballoon assembly can be positioned in the body distal to the desiredstent site. The balloon assembly can then be inflated to anchor theballoon assembly and thus provide support for a guidewire or otherapparatus that can deliver and deploy a stent to the desired stent site.Balloon assemblies in accordance with present disclosure can provideenhanced anchoring characteristics relative to conventional balloonassemblies.

The following example details how an exemplary balloon of the presentdisclosure was constructed.

Example 1: Method of Making the Template with Apertures

An ePTFE film was obtained of the general type as disclosed in U.S. Pat.No. 7,306,729. A discontinuous layer of the thermoplastic FEP (fluoroethylene propylene) was applied to one surface and the film was slitinto a tape. The tape was wrapped around a 6 mm mandrel so that thefilm's machine direction was oriented about the circumference of themandrel. A length of tape was wrapped that resulted in approximately 18layers of film. The tape-wrapped tube was thermally treated in an ovenat 320° C. for 12 minutes. The film tube was removed from the oven andthen removed from the mandrel and cut to 80 mm in length.

The 6 mm tube was placed over a suitable mandrel and square aperturesmeasuring 2 mm by 2 mm were cut through the tube using a CO2 laser,leaving 1 mm of film material between apertures. Six rows of apertureswere cut about the circumference of the tube, parallel to the tube'slongitudinal axis. The pattern was cut over a 60 mm length centered inthe 80 mm tube. This tube is referred to as a “template” with“apertures.”

Example 2: Method of Making a Balloon Assembly Comprising a SizeLimiting Layer Overlaying a Compliant Balloon, Both of which areCircumscribed by a Template with Apertures

An ePTFE film was obtained of the general type as disclosed in U.S. Pat.No. 5,476,589, entitled, “Porous PTFE Film And A Manufacturing MethodTherefore,” which issued Dec. 19, 1995. The film was cut into a tape of25 mm width and helically wrapped about a 9 mm stainless steel mandrelat an 11.4 mm pitch. The wraps were repeated on a bias in oppositedirections to produce an approximately 4-layer film tube.

This tube was then thermally treated in an oven at 380° C. for 9 minutesand then removed from the oven. The tube was removed from the mandrel,placed over a 7 mm mandrel and axially stretched to decrease itsdiameter to 7 mm. A sacrificial ePTFE tape was helically wrapped overthe film tube on the 7 mm mandrel.

The tube assembly was then axially compressed to 85% of its originallength. The tube assembly was then subjected to thermal treatment at380° C. for 1 minute and then removed from the oven. The sacrificialePTFE layer was removed and discarded. The 7 mm tube construct was cutto an 80 mm length. This tube can be referred to as a “size limitinglayer”.

A compliant polyurethane balloon catheter was obtained with a balloonhaving a diameter of 10 mm and length of 60 mm (“COAX,” Bavarian MedizinTechnologies (BMT), Germany).

The size limiting layer was slid over the balloon assembly (with theballoon in its collapsed state). The ends of the size limiting layerwere secured to the catheter using LOCTITE adhesive 4981 (HenkelCorporation, Düsseldorf, 40589 Germany) applied to a 6 mm wide ePTFEtape as it was wrapped 5 times about the size limiting layer tube ends.The balloon was then inflated to an approximate 5 mm diameter.

The template layer, as described in Example 2, was slid over thesize-limiting layer and the compliant balloon (with the balloon at its 5mm diameter). The ends of the template layer were secured to thecatheter using LOCTITE adhesive 4981 applied to a 6 mm wide ePTFE tapeas it was wrapped 5 times about the tube ends. The balloon was theninflated to an approximate 6 mm diameter.

The balloon assembly was then inflated to 4 atmospheres and protrusionsof the underlying compliant balloon were noted extending from theapertures.

Example 3: Method of Making a Balloon Assembly Comprising a SizeLimiting Layer Overlaying a Compliant Balloon, Both of which areCircumscribed by a Template with Apertures Having a First DistensionProfile and a Second Distension Profile

In order to form a distensible template, construct a helically wrapped 8mm film tube using an ePTFE film as described in U.S. Pat. No.7,306,729, issued Dec. 11, 2007. Laser cut the 8 mm film tube to form 2mm×2 mm openings. Reduce the template diameter by stretching thetemplate in a longitudinal direction until the inside diameter of thetemplate reaches approximately 4 mm. Insert a 4 mm mandrel into the 4 mmdrawn down template. Over wrap the template on the 4 mm mandrel with asacrificial film. Longitudinally compress (or scrunch) the over-wrappedtemplate to approximately 60% of the original length. Bake thecompressed template at 380° C. at a time ranging from (0 sec. to 120sec.). This step sets the load at which the template will begin todistend. The lower the baking time, the smaller the load required todistend. Once set, remove the sacrificial film and the template from the4 mm mandrel.

Obtain an inflatable, compliant balloon element constructed to be 8mm×40 mm with a working length of 40 mm, two shoulders of length of 4mm, and two seals of 7 mm, giving it an overall length of 62 mm.

Place an 8 mm×62 mm size limiting layer (constructed in a similar manneras described in Example 2) that has also been drawn down to 4 mm on a 4mm mandrel. Cut the template to a length of (24 mm+7 mm to form theattachment to the size limiting layer at the seal), giving it an overalllength of 31 mm. Slide the cut template over the size limiting layerthat is on the 4 mm mandrel so the inside end of the template alignswith the center line of the size limiting layer. Wrap approximately 5 to20 layers of a porous, sintered, sufficiently thin and strong ePTFEfilm, ½″wide using 4498 LocTite glue to adhere the template at centerline of the size limiting layer. Remove the size limiting layer with thetemplate attached from the 4 mm mandrel.

Place the 4 mm template and size limiting assembly over the compacted 8mm balloon and secure both the proximal and distal ends (7 mm each) bywrapping approximately 10 or more layers of a porous, sintered,sufficiently thin and strong ePTFE film and 4498 LocTite adhesive aroundeach end of the cover and catheter.

In another embodiment, a frangible template can be constructed asdescribed in Example 3, instead using an ePTFE film as described in U.S.Pat. No. 5,814,405 Branca et al., which is hereby incorporated byreference in its entirety.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the present disclosurewithout departing from the spirit or scope of the disclosure. Forexample, while embodiments of the present disclosure have been describedwith reference to the inferior vena cava, embodiments are scaleable andapplications in various central and peripheral vessels and lumens arecontemplated herein. Additionally, the embodiments can be used inconnection with not just humans, but also various organisms havingmammalian anatomies. Thus, it is intended that the embodiments describedherein cover the modifications and variations of this disclosureprovided they come within the scope of the appended claims and theirequivalents.

Benefits, other advantages, and solutions to problems have beendescribed herein with regard to specific embodiments. However, thebenefits, advantages, solutions to problems, and any element orcombination of elements that can cause any benefit, advantage, orsolution to occur or become more pronounced are not to be construed ascritical, required, or essential features or elements of any or all theclaims of the disclosure. Many changes and modifications within thescope of the instant disclosure can be made without departing from thespirit thereof, and the disclosure includes all such modifications.Corresponding structures, materials, acts, and equivalents of allelements in the claims below are intended to include any structure,material, or acts for performing the functions in combination with otherclaim elements as specifically claimed. The scope of the disclosureshould be determined by the appended claims and their legal equivalents,rather than by the examples given above.

What is claimed is:
 1. A balloon assembly comprising a balloon having afirst upper distension limit; a film template having an outer surfaceand extending along at least a portion of the balloon for at least aportion of a working length of the balloon and having a fixed upperdistension limit, the film template including at least one aperture; anda rigid element, the rigid element configured to lay across the at leastone aperture substantially flush with an outer surface of the balloonwhen the balloon is at a first inflated state and to project radiallyoutward when the balloon is at a second inflated state, wherein thefirst upper distention limit of the balloon is greater than the fixedupper distension limit of the film template, wherein the balloonoutwardly protrudes at least partially through the at least one aperturerelative to an outer surface of the film template at the second inflatedstate, the balloon extending the rigid element in a radial directionaway from the outer surface of the balloon as the balloon outwardlyprotrudes at least partially through the at least one aperture relativeto the outer surface of the film template.
 2. The balloon assembly ofclaim 1, wherein the rigid element is integral with the film template.3. The balloon assembly of claim 1, wherein the rigid element is coupledto the film template.
 4. The balloon assembly of claim 1, wherein therigid element comprises a first end having a pointed shape.
 5. Theballoon assembly of claim 1, wherein a therapeutic agent is at leastpartially coated on a surface of the rigid element.
 6. The balloonassembly of claim 1, wherein a therapeutic agent is at least partiallyimbibed on a surface of the rigid element.
 7. The balloon assembly ofclaim 1, wherein the rigid element comprises a bioabsorbable material.8. The balloon assembly of claim 7, wherein the rigid element comprisesa scored portion, and wherein the scored portion is forced by theballoon to break and separate from the template when the balloon is inthe second inflated state.
 9. A balloon assembly comprising: a balloonhaving a first inflated state and a second inflated state; a filmtemplate having an outer surface and extending along at least a portionof a working length of the balloon and having an upper distension limit,the film template including at least one aperture; a rigid elementcoupled to an outer surface of the balloon, the rigid element layingacross the at least one aperture and substantially flush with an outersurface of the balloon at the first inflated state of the balloon andextending radially outward at the second inflated state, wherein thedistention limit of the balloon is greater than the upper distensionlimit of the film template, and wherein the balloon outwardly protrudesthrough the at least one aperture relative to an outer surface of thefilm template at the second inflated state, the balloon extending therigid element outwardly in a radial direction as the balloon outwardlyprotrudes through the at least one aperture relative to the outersurface of the film template.
 10. The balloon assembly of claim 9,wherein the rigid element comprises a lumen.
 11. The balloon assembly ofclaim 10, wherein the lumen is in fluid communication with a fluidmedium.
 12. The balloon assembly of claim 11, wherein the lumen is influid communication with the fluid medium within the balloon.
 13. Theballoon assembly of claim 10, wherein the fluid medium comprises atherapeutic agent.
 14. The balloon assembly of claim 8, wherein asurface of the lumen is partially coated with a therapeutic agent.
 15. Aballoon assembly comprising: a balloon having an inflated state; a filmtemplate having an outer surface and extending along at least a portionof a working length of the balloon and having an upper distension limit,the film template including at least one aperture; an endoprosthes isextending across the at least one aperture of the template along atleast a portion of an outer surface of the template, the endoprosthesisincluding an anchor portion at a first end of the endoprosthesis,wherein the distention limit of the balloon is greater than the upperdistension limit of the film template, wherein the balloon outwardlyprotrudes through the at least one aperture relative to an outer surfaceof the film template at the inflated state, the balloon outwardlyprotruding through the at least one aperture and deploying the anchorportion of the endoprosthesis into a surrounding tissue.
 16. The balloonassembly of claim 15, wherein the endoprosthesis is a stent.
 17. Theballoon assembly of claim 15, wherein the film template comprises ahigh-strength ePTFE.
 18. The balloon assembly of claim 17, wherein thefilm template is inelastic in a direction transverse to a longitudinalaxis of the balloon assembly.
 19. The balloon assembly of claim 15,wherein the film template comprises a first aperture at a first end ofthe film template and a second aperture at a second end of the filmtemplate.
 20. The balloon assembly of claim 15, further comprising asize limiting layer disposed around at least a portion of the balloon.